DESCRIPTION: The overall objective of this proposal is to understand the roles of microglia in the normal adult developing nervous system and under pathophysiological conditions. The proposal describes four aims designed to exploit new findings that microglia express lipocortin 1 (LC1), a calcium-binding protein with anti-inflammatory and immunosuppressive properties. Aim 1 will determine the degree to which LC1 co-localizes with other glia markers under normal conditions and following CNS damage. Aim 2 will examine whether ramified mature microglia are progeny of LC1 positive floor plate glia. Aim 3 will study phosphotyrosine signals in microglia, focusing on phosphorylated LC1 and the phosphotyrosine phosphatase CD-45 that also is present in microglia.The final aim will investigate the characteristics of LC1 microglia in vitro slices and cell cultures under different conditions and in response to stimulation by CSF-1. These studies should provide new insights into the origin and roles of microglia in both normal and challenged CNS conditions.